The DENN domain is a common, evolutionarily ancient, and conserved protein module, yet it has gone largely unstudied; until recently, little was known regarding its functional roles. New studies reveal that various DENN domains interact directly with members of the Rab family of small GTPases and that DENN domains function enzymatically as Rab-specific guanine nucleotide exchange factors. Thus, DENN domain proteins appear to be generalized regulators of Rab function. Study of these proteins will provide new insights into Rab-mediated membrane trafficking pathways.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3077579 | PMC |
| http://dx.doi.org/10.1074/jbc.R110.217067 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Unveiling as a Novel Prognostic Biomarker for Prostate Cancer Recurrence: From Gene to Prognosis.
Biomedicines
December 2024
Department of Pharmacy, China Medical University, Taichung 404, Taiwan.
Prostate cancer is a major global health burden, with biochemical recurrence (BCR) following radical prostatectomy affecting 20-40% of patients and posing significant challenges to prognosis and treatment. Emerging evidence suggests a critical role for differentially expressed in normal and neoplastic cell () domain-containing genes in oncogenesis; however, their implications in prostate cancer and BCR risk remain underexplored. This study systematically evaluated 151 single-nucleotide polymorphisms in domain-containing genes in 458 patients with prostate cancer and BCR, followed by validation in an independent cohort of 185 patients.
View Article and Find Full Text PDFRab11a Controls Cell Shape via C9orf72 Protein: Possible Relationships to Frontotemporal Dementia/Amyotrophic Lateral Sclerosis (FTDALS) Type 1.
Pathophysiology
February 2024
Laboratory of Molecular Neurology, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, Japan.
Abnormal nucleotide insertions of C9orf72, which forms a complex with Smith-Magenis syndrome chromosomal region candidate gene 8 (SMCR8) protein and WD repeat-containing protein 41 (WDR41) protein, are associated with an autosomal-dominant neurodegenerative frontotemporal dementia and/or amyotrophic lateral sclerosis type 1 (FTDALS1). The differentially expressed in normal and neoplastic cells (DENN) domain-containing C9orf72 and its complex with SMCR8 and WDR41 function as a guanine-nucleotide exchange factor for Rab GTP/GDP-binding proteins (Rab GEF, also called Rab activator). Among Rab proteins serving as major effectors, there exists Rab11a.
View Article and Find Full Text PDFDe novo variants in DENND5B cause a neurodevelopmental disorder.
Am J Hum Genet
March 2024
Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy; UOC Genetica Medica, IRCCS Giannina Gaslini, Genoa, Italy.
The Rab family of guanosine triphosphatases (GTPases) includes key regulators of intracellular transport and membrane trafficking targeting specific steps in exocytic, endocytic, and recycling pathways. DENND5B (Rab6-interacting Protein 1B-like protein, R6IP1B) is the longest isoform of DENND5, an evolutionarily conserved DENN domain-containing guanine nucleotide exchange factor (GEF) that is highly expressed in the brain. Through exome sequencing and international matchmaking platforms, we identified five de novo variants in DENND5B in a cohort of five unrelated individuals with neurodevelopmental phenotypes featuring cognitive impairment, dysmorphism, abnormal behavior, variable epilepsy, white matter abnormalities, and cortical gyration defects.
View Article and Find Full Text PDFDENND6A links Arl8b to a Rab34/RILP/dynein complex, regulating lysosomal positioning and autophagy.
Nat Commun
January 2024
Department of Neurology and Neurosurgery, Montreal Neurological Institute (the Neuro), McGill University, Montreal, QC, Canada.
Lysosomes help maintain cellular proteostasis, and defects in lysosomal positioning and function can cause disease, including neurodegenerative disorders. The spatiotemporal distribution of lysosomes is regulated by small GTPases including Rabs, which are activated by guanine nucleotide exchange factors (GEFs). DENN domain proteins are the largest family of Rab GEFs.
View Article and Find Full Text PDFHepatitis B virus evades the immune system by suppressing the NF-κB signaling pathway with DENND2A.
Microbiol Spectr
March 2024
Research Department, Purotech Bio Inc, Yokohama, Kanagawa, Japan.
Overcoming hepatitis B virus (HBV) is a challenging problem because HBV deceives the host immune system. We have found that DENN domain-containing 2A (DENND2A) was essential for HBV maintenance, although its role remains unclear. In this study, we elucidate its function by screening a novel DENND2A-binding peptide, DENP4-3S.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!